We studied 30 patients (15 males and 15 females; 55.6 +/- 1.3 yrs) with RH on a combined (lisinopril/amlodipine/hydrochlorothiazide) therapy. Salt loading (SL) was performed via infusion of 1000 mL saline i.v. for 1 hour. Beat-to-beat BP was registered using Finometer Pro device. Arterial stiffness was measured by Sphygmocor Px device with a calculation of pulse wave velocity (PWV). Levels of MBG were estimated by fluoroimmunoassay and by activity of NKA in erythrocytes at baseline and following SL, measured in the absence and in the presence of a monoclonal anti-MBG antibody (mAb) ex-vivo treatment. Within 2 hrs of SL patients exhibited elevation of systolic and diastolic BP (175 +/- 5 vs. 152 +/-3 and 101 +/- 2 vs. 90 +/- 2 mmHg, both P<0.01), increase in plasma MBG (0.48 +/- 0.06 vs. 0.31 +/- 0.05 nmol/L), and NKA inhibition (1.49 +/- 0.09 vs. 2.11 +/- 0.07 umol Pi/ml/hr; P<0.01). Anti-MBG mAb ex-vivo restored NKA (2.7 +/- 0.1 umol Pi/ml/hr; P<0.01). In patients of both sexes magnitude of pressor response to SL did not correlate with the levels of MBG and with NKA activity, but magnitude of MBG-induced NKA inhibition and of SL-stimulated MBG was positively associated with PVW in male (r=0.55, P=0.03, and r=0.51, P=0.03, respectively), but not in female subjects (r=0.15, P=0.57, and r=0.22, P=0.41, respectively). In patients of both sexes magnitude of MBG-induced NKA inhibition was positively associated with age (r=0.45; P=0.006). These results indicate that in male patients with resistant hypertension magnitude of MBG-induced NKA inhibition associates not with the salt-sensitivity of BP per se, but with age of patients and with PVW, which characterizes vascular stiffness, a major feature of cardiovascular aging.